Campylobacter is one of the most common cause of diarrhea worldwide. Human milk protects young infants against Campylobacter diarrhea by several factors including fucosylated oligosaccharides. However, there is a lack of understanding of the chemical structure of these components and their mechanism of interaction with Campylobacter virulence traits associated with attachment to gut mucosa. The specific aims of this project are: 1) define the virulence markers of Campylobacter associated with attachment to epithelial cells; 2) characterize and purify milk glycoconjugates that inhibit Campylobacter infection; 3) assess passive protection in breast- fed children and experimentally in transgenic mice carrying a human fucoslytransferase gene expressed mainly in mammary tissue; 4) develop strategies for large-scale synthesis of fucosylated glycoconjugates active against Campylobacter infection; and 5) conduct clinical trials on safety and protection of fucosylated glycoconjugates against Campylobacter diarrhea. The long-term goal of this project is to develop methods for prevention and treatment of Campylobacter infection through understanding at the cellular and molecular level the mechanism of protection conferred by human milk against Campylobacter infection.